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Advances in Pancreatic Cancer — and Symptoms to Know

Survival rates have risen, and there are new treatments, but early diagnosis is key

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En español | Twenty years ago, getting a pancreatic cancer diagnosis was very often devastating. The cancer usually wasn't caught until later stages, partly because the pancreas is tucked behind the stomach, making it hard to detect tumors. The five-year survival rate for this kind of cancer was around 4 percent. Doctors were able to offer patients only standard chemotherapy, radiation and/or a risky surgery.

Today, however, the five-year survival rate for pancreatic cancer has more than doubled. If the disease is caught at stage 1, the survival rate is 39.4 percent, according to the National Cancer Institute (NCI).

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Early Warning Signs of Pancreatic Cancer

If your pancreatic cancer is caught at an early stage, you have a higher chance of a cure and can better tolerate treatment, says Wolpin of the Dana-Farber Cancer Institute. That's why you should watch out for the following symptoms.

Abdominal and back pain

The most common symptom of pancreatic cancer is abdominal discomfort in the mid to upper abdomen, above the belly button, that often radiates to the back. This kind of pain can also be experienced by people with ulcers and gallstones, or even reflux. The typical pain associated with pancreatic cancer, however, can be very dull at first but become very severe and persistent, explains James Farrell, M.D., director of the Yale Center for Pancreatic Diseases at Yale Cancer Center.

Diabetes with weight loss

Another sign is new onset diabetes or worsening of blood sugar, especially paired with unexplained weight loss, says Wolpin, senior author of a study on the topic published in JAMA Oncology in August.

He and his research team found that recent onset diabetes was associated with a threefold higher risk of pancreatic cancer. The incidence rates for this type of cancer were six- to tenfold higher among study participants with newly diagnosed diabetes and weight loss, compared with participants without diabetes or weight loss.

Darkening of urine and lightening of stool; jaundice; itching

Sometimes pancreatic cancer can obstruct the duct that contains bile, a fluid the liver secretes that aids in absorption of nutrients. When the duct gets blocked, it can cause a backup of bile that may get into the bloodstream, causing jaundice (yellowing of the skin and eyes), darkening of urine, lightening of stool, and, less commonly, itching.

Nausea and vomiting

It can be hard to tell whether these symptoms are indications of pancreatic cancer or the result of something like food poisoning or a new medication. “If the symptoms are new, don't resolve after 24 hours and result in excess dehydration, or if they progress, medical attention should be sought,” Farrell advises.

Fatigue

People with this cancer often experience lethargy. “It's not the kind of severe fatigue you get with the flu,” Wolpin observes. Instead, you become less active and feel like you can't do as much as you used to and become more tired at the end of the day.

Loss of appetite and unintentional weight loss

Often patients with pancreatic cancer start eating less, in part because they don't feel well. They can also feel bloated or fuller sooner after eating. Take note if these symptoms seem to get worse over time, Wolpin says.

A surge in research funding is partly responsible for this good news. For example, NCI money for pancreatic cancer research rose from $17 million in 1999 to more than $178 million in 2017. Funding by other agencies and organizations has made similar leaps.

With stronger support, pancreatic cancer research is making huge advances. Scientists are developing new ways to screen for this cancer. They are able to target some tumors with off-label chemotherapy. In the clinic, oncologists are successfully combining multiple forms of chemotherapy and using drugs that have been approved for patients with other cancers. And, they are finding ways to deliver more focused radiation to tumors to shrink them, which can make removal easier.

"This is an exciting time in cancer research,” says Udo Rudloff, M.D., a senior investigator at the Center for Cancer Research, NCI. “To keep making a difference in pancreatic cancer, we need a combination approach — novel basic science research and also strategies for bringing these findings to the clinic to help our patients.”

Here are a few of the latest treatments and advances.

The great promise of targeted therapy

About 25 percent of pancreatic cancer patients have unique molecular alterations in their tumor. Now researchers can study these differences using technologies such as molecular profiling, which will allow doctors to target treatments individually. A large study recently published in The Lancet Oncology found that pancreatic cancer patients who received tailored drug therapy based on their tumor's unique characteristics lived an average of one year longer than those who did not receive targeted therapy.

In 2018, a year after being diagnosed with pancreatic cancer, Karen Kiernan, 63, a retired nurse from Naperville, Illinois, received such a targeted therapy with Keytruda, a drug that is approved for lung and other cancers. By then, Kiernan had severe back pain from her cancer and had lost 40 pounds. But once she began taking Keytruda, she was able to regain some weight. Now, she says, she is “doing everything I used to do before I had cancer.” Her condition has not progressed since she began treatment two years ago, and her doctors think she may be a candidate for surgery.

But Kiernan's is a success story that fewer than 50 percent of pancreatic cancer patients experience. Most patients, says Michael Pishvaian, M.D., director of the Gastrointestinal, Developmental Therapeutics and Clinical Research Programs at the Kimmel Cancer Center Johns Hopkins University School of Medicine, are not referred to any treatment at all because of what he calls “tremendous cynicism” about its benefits. The Lancet research, he says, should be “a call to action to test every pancreatic cancer patient's tumor."

Using the breast cancer drug Lynparza

Mary Phillips, 59, was diagnosed with metastatic pancreatic cancer in March 2016. At first she took the latest combination chemotherapy for pancreatic cancer. Then she enrolled in a clinical trial of the drug Lynparza. Because the medication was already being used by some patients with breast or ovarian cancer (those with a mutation in their BRCA or DNA repairing genes), researchers thought that it could be useful for pancreatic cancer patients with the same mutations.

Early findings in this area have been promising. A 2019 study, published in The New England Journal of Medicine, reported that patients with such a BRCA mutation who took Lynparza for metastatic pancreatic cancer had no new tumor growth, nor spread of their cancer, for twice as many months as those not receiving the drug. Still, there was no difference in long-term survival past 18 months. In December 2019 the Food and Drug Administration (FDA) approved the medication for maintenance therapy for this group of patients.

Delivering more with guided radiation therapy

Norman Kravetz, 71, of Boynton Beach, Florida, was diagnosed with pancreatic cancer last year. He had six months of intensive chemotherapy, followed by cutting-edge MRI-guided radiation therapy at Dana-Farber/Brigham and Women's Cancer Center in Boston, Massachusetts. The new technology combines two ways of targeting the tumor to increase precision.


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Without MRI guidance, radiation therapy can be technically challenging because of the location of the pancreas in the middle of the abdomen. “MRI guidance allows us to visualize and accurately deliver radiation treatment in order to treat the tumor with high doses of radiation while reducing the radiation dose to nearby vital structures, thereby reducing the risk of side effects,” explains Joseph Mancias, M.D., Kravetz's radiation oncologist.

After the six months of chemo and just one week of the new radiation treatment (usually available at major medical centers across the country), Kravetz saw his tumor shrink and he was able to have surgery to remove it. Now his gym membership is expiring, and if he re-ups for two years, he gets one year free. His doctor told him to “go for it,” he says.

Using artificial intelligence to read scans

Early pancreatic cancer can be subtle enough that it's missed on scans 30 percent of the time, which means that around half of all cases aren't caught until later stages, as was true with Jeopardy! host Alex Trebek, who died of the disease last month. “We should be able to do better,” says Elliot Fishman, M.D., professor of radiology and radiological science at Johns Hopkins School of Medicine in Baltimore, Maryland. To that end, Fishman is using artificial intelligence to teach the computer to read CT scans to detect tumors at earlier stages so they can be surgically removed. (Currently, only 15 to 20 percent of pancreatic cancer patients are candidates for surgery.)

So far, Fishman has screened several thousand pancreatic cancer patients with his technology and has been able to detect tumors more than 90 percent of the time.

Using blood and urine screenings to detect cancer early

As is done for many other cancers, a simple blood or urine test may one day be used to screen for pancreatic cancer in its earliest stages, since body fluids contain bits of DNA from tumor cells. Research teams are developing methods of blood-based DNA analysis to detect pancreatic cancer with high accuracy, says Brian Wolpin, M.D., associate professor of medicine at Harvard Medical School and director of the GI Cancer Center at Dana-Farber.

“Scientists have made quite a bit of progress in the last five years in developing these multi-cancer early-detection tests, and large studies are now ongoing to define their utility,” says Wolpin, who notes that such procedures may be able to detect cancerous tissue 90 percent of the time. Meanwhile, in clinical trials in the U.K. and Finland, researchers are studying urine analysis to detect pancreatic cancer this way.

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Know — and Lower — Your Risk Factors for Pancreatic Cancer

"Increasing awareness of the risk factors associated with pancreatic cancer development, such as having a family history of pancreatic cancer, having a pancreas cyst on a CT or MRI scan, or developing new onset diabetes, offer the opportunity for us to diagnose pancreatic cancer early and intervene, with the overall hope of improving patient outcome overall,” says Farrell of the Yale Center for Pancreatic Diseases at Yale Cancer Center.

You can lower your risk for pancreatic cancer by changing unhealthy lifestyle factors you can control, such as smoking, drinking and being overweight.

About 25 percent of pancreatic cancers are thought to be caused by cigarette smoking. Cigar smoking and smokeless tobacco raise your risk, too, according to the American Cancer Society (ACS).

People who are obese (BMI of 30 or higher) are about 20 percent more likely to develop pancreatic cancer, according to the ACS. Type 2 diabetes is more common among overweight adults, and this condition raises the risk for pancreatic cancer, too, especially in those over 50 who suddenly develop type 2 without a family history of it, says Wolpin.

Drinking alcohol can lead to chronic pancreatitis, or inflammation of the pancreas, which has been linked to an increase in pancreatic cancer.

Certain risk factors for pancreatic cancer can't be changed, but they're important to know, and you should share them with your doctor.

About 10 percent of pancreatic cancers are thought to be the result of genetics. If you have a family history of the disease, talk with your doctor about whether you should be screened for it.

A family history of other cancers and syndromes can also raise your risk for pancreatic cancer, such as hereditary breast and ovarian cancer caused by BRCA1 or BRCA2 mutations, and Lynch syndrome.

Data have been mixed about whether long-term use of proton pump inhibitors to reduce stomach acid, or infection with Helicobacter pylori (a bacteria that can cause ulcers), increases the risk of pancreatic cancer, Wolpin says.

Other risk factors include age, gender and race. Men develop pancreatic cancer slightly more than women. The risk of developing it increases with age. African Americans are more likely to get pancreatic cancer than any other racial group.

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